|
|
|
| Morpholine hydrazone scaffold: Synthesis, anticancer activity and docking studies |
| Muhammad Tahaa,b, Syed Adnan Ali Shaha,c, Muhammad Afifia,c, Manar Zulkefleec, Sadia Sultana,c, Abdul Wadoodd, Fazal Rahime, Nor Hadiani Ismaila,b |
a Atta-ur-Rahman Institute for Natural Product Discovery(AuRIns), Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;
b Faculty of Applied Science, UiTM Shah Alam, 40450 Shah Alam, Selangor D. E., Malaysia;
c Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor D. E., Malaysia;
d Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan;
e Department of Chemistry, Hazara University, Mansehra 21300, Pakistan |
|
|
|
|
Abstract In this paper, synthesis and anticancer activities of morpholine hydrazones scaffold (1-17) thoroughly studied. Small series of morpholine hydrazones synthesized by treating 5-morpholinothiophene-2-carbaldehyde with different aryl hydrazides to form morpholine hydrazones scaffold (1-17). The in vitro anticancer potential of all these compounds was checked against human cancer cell lines like HepG2 (human hepatocellular liver carcinoma) and MCF-7 (human breast adenocarcinoma). Analogs 13 had similar substantial cytotoxic effects towards HepG2 with IC50 value 6.31±1.03 μmol/L when compared with the standard Doxorubicin (IC50 value 6.00±0.80 μmol/L); while compounds 5,8 and 9 showed potent cytotoxicity against MCF-7 with IC50 value 7.08±0.42 μmol/L, 1.26±0.34 μmol/L and 11.22±0.22 μmol/L respectively when compared with the standard Tamoxifen (IC50=11.00±0.40 μmol/L). Molecular docking studies also performed to understand the binding interaction.
|
|
Received: 17 June 2016
|
| Fund:Syed Adnan Ali Shah would like to acknowledge the Ministry of Higher Education (MOHE) for financial support under the Fundamental Research Grant Scheme (FRGS) with sponsorship reference numbers FRGS/1/2015/SG05/UiTM/02/6. The author would also like to acknowledge Universiti Teknologi MARA for the financial support under the reference number 600-RMI/FRGS 5/3 (135/2015). |
|
Corresponding Authors:
Muhammad Taha, Syed Adnan Ali Shah
E-mail: muhamm9000@puncakalam.uitm.edu.my;syedadnan@salam.uitm.edu.my,benzene301@yahoo.com
|
|
|
|
| [1] |
C. Duncan, A.R. White, Copper complexes as therapeutic agents, Metallomics 4(2012) 127-138.
|
| [2] |
C.Y. Ang, S.Y. Tan, Y.L. Zhao, Recent advances in biocompatible nanocarriers for delivery of chemotherapeutic cargoes towards cancer therapy, Org. Biomol. Chem. 12(2014) 4776-4806.
|
| [3] |
A. Garza-Ortiz, P.U. Maheswari, M. Siegler, A.L. Spek, J. Reedijk, A new family of Ru(II) complexes with a tridentate pyridine Schiff-base ligand and bidentate co-ligands:synthesis, characterization, structure and in vitro cytotoxicity studies, New J. Chem. 37(2013) 3450-3460.
|
| [4] |
W.S. Chen, W.Z. Ou, L.Q. Wang, et al., Synthesis and biological evaluation of hydroxyl-substituted Schiff-bases containing ferrocenyl moieties, Dalton Trans. 42(2013) 15678-15686.
|
| [5] |
F.U. Rahman, A. Ali, R. Guo, et al., Synthesis and anticancer activities of a novel class of mono-and di-metallic Pt(II) (salicylaldiminato) (DMSO or Picolino) Cl complexes, Dalton Trans. 44(2015) 2166-2175.
|
| [6] |
C.L. Sawyers, C. Abate-Shen, K.C. Anderson, et al., AACR cancer progress report 2013, Clin. Cancer Res. 19(2013) S1-S98.
|
| [7] |
V. Ribrag, J. Dupuis, H. Tilly, et al., A dose-escalation study of SAR3419, an antiCD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, Clin. Cancer Res. 20(2014) 213-220.
|
| [8] |
M. Ghoussaini, O. Fletcher, K. Michailidou, et al., Genome-wide association analysis identifies three new breast cancer susceptibility loci, Nat. Genet. 44(2012) 312-318.
|
| [9] |
N.J. Robert, V. Diéras, J. Glaspy, et al., RIBBON-1:randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer, J. Clin. Oncol. 29(2011) 1252-1260.
|
| [10] |
B. Rosenberg, L. Van Camp, T. Krigas, Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode, Nature 205(1965) 698-699.
|
| [11] |
A. Sak, S. Grehl, M. Engelhard, et al., Long-term in vivo effects of cisplatin on γ-H2AX foci signaling in peripheral lymphocytes of tumor patients after irradiation, Clin. Cancer Res. 15(2009) 2927-2934.
|
| [12] |
L. Galluzzi, L. Senovilla, I. Vitale, et al., Molecular mechanisms of cisplatin resistance, Oncogene 31(2012) 1869-1883.
|
| [13] |
M. Andrs, J. Korabecny, D. Jun, et al., Phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositol 3-kinase-related kinase (PIKK) inhibitors:importance of the morpholine ring, J. Med. Chem. 58(2015) 41-71.
|
| [14] |
C. Dugave, L. Demange, Cis-trans isomerization of organic molecules and biomolecules:implications and applications, Chem. Rev.103(2003) 2475-2532.
|
| [15] |
A. Arrieta, D. Oteagui, A. Zubia, et al., Solvent-free thermal and microwaveassisted[3+2] cycloadditions between stabilized azomethine ylides and nitrostyrenes. An experimental and theoretical study, J. Org. Chem. 72(2007) 4313-4322.
|
| [16] |
A. Polak, Mode of action of morpholine derivatives, Ann. N. Y. Acad. Sci. 554(1988) 221-228.
|
| [17] |
A. Kerkenaar, The model of action of dimethylmorpholines, Recent Trends in Discovery, Development and Evaluation of Antifungal Agents, vol. 1, Prous Science Publ., 1987, pp. 523-542.
|
| [18] |
R.G.M.P. Pinto, B.V. Silva, A.C. Pinto, Syntheis of convolutamidin analogues, 35th Annual Meeting of the Brazilian Chemical Society (2013).
|
| [19] |
M. Taha, N.H. Ismail, S. Imran, et al., Identification of bisindolylmethanehydrazone hybrids as novel inhibitors of β-glucuronidase, DFT, and in silico SAR intimations, RSC Adv. 6(2016) 3276-3289.
|
| [20] |
M. Taha, N.H. Ismail, S. Imran, M. Selvaraj, F. Rahim, Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies, RSC Adv. 6(2016) 3003-3012.
|
| [21] |
S. Imran, M. Taha, N.H. Ismail, et al., Synthesis, in vitro and docking studies of new flavone ethers as α-glucosidase inhibitors, Chem. Biol. Drug Des. 87(2016) 361-373.
|
| [22] |
M. Taha, N.H. Ismail, S. Imran, et al., Hybrid benzothiazole analogs as antiurease agent:synthesis and molecular docking studies, Bioorg. Chem. 66(2016) 80-87.
|
| [23] |
M. Taha, N.H. Ismail, S. Imran, et al., Novel thiosemicarbazide-oxadiazole hybrids as unprecedented inhibitors of yeast α-glucosidase and in silico binding analysis, RSC Adv. 6(2016) 33733-33742.
|
| [24] |
M. Taha, N.H. Ismail, S. Imran, et al., Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles, Bioorg. Chem. 66(2016) 117-123.
|
| [25] |
A. Kaapro, J. Ojanen, Protein Docking. Available at http://www.lce.hut.fi/teaching/S-114.500/k2002/Protdock.pdf, 2002.
|
| [26] |
M. Taha, N.H. Ismail, A. Khan, et al., Synthesis of novel derivatives of oxindole, their urease inhibition and molecular docking studies, Bioorg. Med. Chem. Lett. 25(2015) 3285-3289.
|
| [27] |
M. Taha, N.H. Ismail, S. Imran, et al., Novel quinoline derivatives as potent in vitro α-glucosidase inhibitors:in silico studies and SAR predictions, Med. Chem. Comm. 6(2015) 1826-1836.
|
| [28] |
M.Taha,N.H.Ismail,S.Lalani,etal.,Synthesis of novel inhibitors of α-glucosidase based on the benzothiazole skeleton containing benzohydrazide moiety and their molecular docking studies, Eur. J. Med. Chem. 92(2015) 387-400.
|
| [1] |
Hai-Jiang Chen, Yan-Juan Jiang, Yong-Qiang Zhang, Qi-Wei Jing, Na Liu, Yan Wang, Wan-Nian Zhang, Chun-Quan Sheng. New triazole derivatives containing substituted 1, 2, 3-triazole side chains: Design, synthesis and antifungal activity[J]. CCL, 2017, 28(04): 913-918. |
|
|
|
|
